Multifunctional acrylates used as cross-linkers in dental and biomedical self-etching bonding adhesives

ABSTRACT

This invention describes an adhesive used for bonding dental and medical biomaterials to hard tissues via a molecular bridge formed from calcium-reactive amines and acrylic or methacrylic ester monomers to hard tissues such as enamel, dentin, and bone. This formulation consists of an acid-stable polymerizable compound with multi-functional acrylate cross-linkers. This formula provides good self-adherence without prior preparation of the hard tissue substrates. The formulation can contain chemical- and/or light-activated free-radical initiators.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. patent application Ser. No.12/362,622 filed Jan. 30, 2009, which claims priority to U.S. PatentApplication No. 60/025,045 filed Jan. 31, 2008.

BACKGROUND OF INVENTION

1. Field of Invention

This invention relates to a biomaterial and more specifically a highmolecular weight, multifunctional acrylate cross-linking compositionthat, when formulated with other compounds will self-etch andself-adhere to hard tissues, such as enamel, dentin, and bone.

2. Description of the Related Art

The use of synthetic materials to expedite healing is becoming morewidespread. A burgeoning area of growth is the use of relatively inerthardening agents for use as adhesives or as a substitute for hardtissue. Hard tissue typically means tissues that have becomemineralized, or tissue having a firm intercellular substance, such asenamel, dentin, cartilage, and bone. Bone and tooth structure, such asenamel, dentin and cementum, have certain compositional and morphologicsimilarities. Like enamel and dentin, bone consists primarily ofinorganic material, which is almost exclusively in the form of anapatite of calcium and phosphate that resembles hydroxylapatite, and alesser amount of organic material, which is 90% collagen. Morphologicsimilarities also exist. Enamel and dentin both contain tubules whichmeet their respective surfaces at a perpendicular angle, while bonecontains tube-like Haversian Canals. The Haversian Canals run parallelto the bone's surface, but Volkmann's Canals, which run from them meetthe bone surface at a perpendicular angle.

Teeth that are fractured or have lost dental restorations often involveexposed dentin. These exposed teeth are prone to tooth decay, andpatients usually experience pain. For treatment purposes, the exposedteeth are usually restored with permanent dental restorations. However,definitive dental restorations often are not performed in a timelyfashion. In these cases, temporary dental restorations (fillings) areusually placed onto the exposed teeth. There are a variety ofrestorative dental materials that can be used as temporary fillings.

The materials most commonly chosen as temporary fillings are zincoxide-eugenol (ZOE) compounds, glass-ionomer materials, and resin-baseddental materials. These filling materials are retained in teeth throughmechanical retention and/or chemical bonding with the tooth structure.

ZOE fillings require mechanical retention. These materials arerelatively weak compared to the other types of temporary fillingmaterials.

Glass-ionomer dental filling materials can bond to tooth structurewithout the need of a separately applied bonding agent. In addition,glass-ionomer materials release fluoride, which strengthens the surfaceof the tooth. A disadvantage of glass-ionomer dental filling materialsis their relatively long setting time and concomitant sensitivity tomoisture. Moisture exposure can result in premature disintegration ofthe glass-ionomer material and reduce bond strength. Furthermore, thechemical bond formed between glass-ionomers and tooth structure isrelatively weak.

Resin-based filling materials can be bond to teeth using both mechanicaland chemical retentions. Bonding of resin-based dental materials totooth structure is currently achieved through a multi-step process. Adentin-enamel bonding agent must be applied to the tooth prior toplacing the dental material. Applying this bonding agent often requiresmultiple steps and a significant amount of clinical time. Misapplicationof the bonding material may also occur.

In general, retention of temporary fillings through chemical bonding isquicker, requires less preparation of the tooth, and is usuallystronger. Often teeth can be temporarily restored with dental materialsusing only chemical bonding. Acid etching of the tooth surface are oftenperformed to improve adhesion of resin-based filling materials bypromoting mechanical retention. However, many acid-etching agents mustbe removed prior to application of the bonding agents, which furtherincreases clinical time. Acid etching can also cause dental sensitivityin some patients.

There are dental restorative materials on the market that areself-etching adhesives. These compositions generally use water and/ororganic solvents and take a liquid form. Consequently, theseself-etching adhesives have a short shelf-life, which may poseadditional problems for storage. For example, these materials mayexperience a premature setting in extreme conditions such as thosepresented in a desert battlefield. Furthermore, many of theseformulations require multiple applications of a single component orapplication of several separate components. Therefore, they require moreclinical time to apply than the inventive formulation.

U.S. Pub. No. 2007/0244215 A1 by Junjie Sang, describes a one-componentself-etching dental adhesive, which requires a simple one-coatapplication, without the need of separate acid-etching, priming orbonding step. This is achieved through the employment of ahydrolytically stable, acidic, high-strength adhesive monomer (such asPENTA) with a stable, bifunctional, hydrophilic monomer (such as AHPMA)that yields greater cross-linking. However, this material lacks fillercontent and does not provide a fluoride source.

U.S. Pub. No. 2007/0155853 A1 by Chen et al., is another one-componentself-etching self-priming dental adhesive composition. The formulationcontains BisGMA(2,2-bis[4-(2-hydroxy-3-methacryloylpropoxy)-phenyl]-propane), DPPA(dipentaerythrytol pentaacrylate), GDM (glycerol dimethacrylate), GPDM(glycerol phosphate dimethacrylate), and PMGDM (pyromellitic glyceroldimethacrylate). The formulation contains both water and an organicsolvent such as acetone or ethanol. Additional clinical steps and resinmaterials are required to bond composite resins to dentin or enamel.

U.S. Pub. No. 2006/0069181 by Thalaker et al. presents a liquidself-etch adhesive that is composed of a carboxylic acid functionalpolymer and water. This dental adhesive composition consists of twoliquid components and contains no fluoride releasing agents or glassfillers. Additional clinical steps and resin materials are required tobond composite resins to dentin or enamel.

U.S. Pub. No. 2007/0248927 A1 by Luchterhandt et al. is a self-adhesivecomposition based on polyacrylate, Kayamer, MH-P (Methacryloxyhexylphosphate), MO-P (8-Methacryloxyoctyl phosphate), and MD-P(10-Methacryloxydecyl phosphate) polymerizable compounds. This formulais only photo-curable and requires additional priming step and curingequipment.

U.S. Pub. No. 2007/0203257 A1 by Xuejun Qian, describes a two-partpaste/paste self-etch adhering dental composition based on UDMA(reaction product of 2-hydroxyethyl methacrylate with2,4,4-trimethylhexane diisocyanate), BisGMA, GDM-P(glyceryldimethacrylate phosphate), and GDM (glyceryidimethacrylate). Italso contains a solvent, which may increase the oxidation rate of theformula. The formula does not contain any fluoride releasing agent.

U.S. Pub. No. 2005/0277706 A1 by Han et al., describes a highlyfunctional dental adhesive that is based on multifunctional pre-polymermixture of BisGMA, Tri-GMA, 4-MBTA (4-methacryloxybutyltrimelliticanhydride), MDP, HPMA and water. This adhesive is only photo-curable,which requires additional curing equipment. In addition, this formulacontains a maximum of five percent filer material and does not include afluoride releasing agent.

SUMMARY OF THE INVENTION

The current invention aims to improve existing technology. The inventiveformulation has multiple advantages over the prior art. It is aself-etching material, which can be applied to tooth in a single stepwithout the need of a primer. The inventive formulation is alsodual-curable, which means it can be photo-cured or chemically hardened.Chemical setting allows for curing in deep areas where light is noteffective and eliminates the need of additional equipment in situationswhere such equipment are not readily available. Furthermore, theinventive formula contains fluoride releasing materials and up to 75% ofglass fillers in a combination of different particle sizes. Theinclusion of fluoride releasing agent and high percentage of glassparticles of varying sizes improve physical and mechanical properties ofthe final set material. Additionally, the inventive formula is a powerand liquid combination format and contains no solvent, which mayincrease shelf-life and prevents premature setting.

An object of this invention is an acid-stable polymerizable compositionwith multi-functional acrylate cross-linkers suitable as adental/biomedical self-adhesive bonding material.

Another object of the invention is a self-etching, acid-stablepolymerizable composition with multifunctional acrylate cross-linkers,which provides good self-adherence without prior preparation of the hardtissue or the substrates.

An additional object of the invention is a self-etching, acid-stablepolymerizable adhesive material, which contains chemical and/orlight-activated free-radical initiators that allows the final materialto set within a relatively short time, approximately 4-4.5 minutes at37° C.

A further object of the invention is a fluoride-releasing compositionthat can be used as a self-etching, self-adhesive bonding agent betweenhard tissues (enamel, dentin, or bone) and dental and biomedicalsubstrates.

Another object of this invention is a method of bonding dental andmedical biomaterials via a molecular bridge formed from calcium reactiveamines and acrylic or methacrylic ester monomers to hard tissues such asenamel, dentin, and bone.

DETAIL DESCRIPTION OF THE INVENTION

This invention is directed to an adhesive composition that can be usedin bonding dental and medical biomaterials to hard tissues via amolecular bridge formed from calcium reactive amines and acrylic ormethacrylic ester monomers contained in the biomaterials and enamel,dentin, and bone. The adhesive composition may be used as: (i) temporarydental restorative or dressing material, (ii) long-term dentalrestorative (filling) material through the incorporation of variousinorganic filler materials, (iii) luting cement, for bonding fixeddental prosthetic devices, such as crowns and bridges, to dentin andenamel, or (iv) luting cement for bonding orthodontic brackets toenamel; (v) stint for stabilizing avulsed, inverted, or luxated teeth;(vi) bone cement, for bonding implant prostheses and skull implants tobone; (vii) liner or base under amalgam dental restorations.

This adhesive composition comprises of an acid-stable polymerizablecompound with multi-functional acrylate cross-linkers and provides goodself-etching and self-adherence without prior preparation of the hardtissue substrates, such as separate acid etching or priming steps. Ingeneral, the adhesive composition comprises a mixture of one or morepolymerizable acrylic or methacrylate compounds, one or more hydrophilicacrylate or methacrylate compounds, one or more calcium reactive amines,one or more acrylic or methacrylic esters, one or more polymerizationinitiators, glass powder, fluoride-containing compounds, and otherfilter materials. The esters functions both as an acrylic ormethacrylate compound that polymerizes with the other a acrylic ormethacrylate compounds and as a cross-linker, which forms a salt bridgewith calcium in the dentin or enamel. The preferred composition couldvary slightly for different dental and biomedical applications.Considerations would include varying the formula to affect propertiessuch as viscosity, flowability, working time, setting time, filmthickness, and bond strength. Standard mechanical and material testingmay be performed to assess these formulations for their designedapplication. In general, the laboratory tests that may be performed tomeasure the physical and mechanical properties of the inventivecompound, which include compressive strength, DTS, flexural strength,shear bond strength, and film thickness. One of skill in the art willappropriate that the above material properties can be adjusted asappropriate for each dental/biomedical application.

In a preferred embodiment, the composition contains two components: aliquid component and a powder component. The liquid component containsat least one polymerizable acrylic or methacrylate compound, and one ormore hydrophilic acrylate or methacrylate compounds. Examples ofsuitable hydrophilic acrylates are 2-hydroxyethyl acrylate andhydroxypropyl acrylate. An example of a hydrophilic methacrylatecompound is hydroxyethylmethacrylate (HEMA). Examples of polymerizableacrylates are: ethyl acrylate, propyl acrylate, isopropyl acrylate,2-hydroxyethyl acrylate, hydroxypropyl acrylate, tetrahydrofurfurylacrylate, glycidyl acrylate, glycerol mono- and di-acrylate,ethyleneglycol diacrylate, polyethyleneglycol diacrylate, neopentylglycol diacrylate, trimethylolpropane triacrylate, mono-, di-,tri-acrylate, mono-, di-, tri-, and tetra-acrylates of pentacrythritoland dipentaerythritol, 1,3-butanediol diacrylate,1,4-butanedioldiacrylate, 1,6-hexane diol diacrylate, 2,2%bis[3(4-phenoxy)-2-hydroxypropane-1-acrylate]propane,2,2′bis(4-acryloxyphenyl)propane,2,2′-bis[3(4-phenoxy)-2-hydroxypropane-1-acrylate]propane,dipentaerthritol pentaacrylate esters (SR 399) and dipentaerthritolpentaacrylate esters (SR 399 LV).

Polymerizable methacrylate compounds may be: methacrylates, ethylmethacrylate, propyl methacrylate, isopropyl methacrylate,tetrahydrofurfuryl methacrylate, glycidyl methacrylate, the diglycidylmethacrylate of bis-phenol A(2,2-Bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl]propane) (BisGMA),glycerol mono- and di-methacrylate, ethyleneglycol dimethacrylate,polyethyleneglycol dimethacrylate, triethylene glycol dimethacrylate(TEGDMA), neopentylglycol dimethacrylate, trimethylol propanetrimethacrylate, mono-, di-, tri-, and tetra-methacrylates ofpentacrythritol and dipentaerythritol, 1,3-butanediol dimethacrylate,1,4-butanediol dimethacrylate, Bis[2-(methacryloyloxy)ethyl]phosphate(BisMEP),1,6-hexanediol dimethacrylate,2-2′-bis(4-methacryloxyphenyl)propane,2,2′-bis[4(2-hydroxy-3-methacryloxy-phenyl)]propane, 2,2′bis[4(2-hydroxy-3acryloxyphyenyl)propane,2,2′-bis(4-methacryloxyethoxyphenyl)propane,2,2′-bis(4-acryloxyethoxyphenyl)propane,2,2′-bis(4-methacryloxypropoxyphenyl)propane,2,2′-bis(4-acryloxypropoxyphenyl)propane,2,2′-bis(4-methacryloxydiethoxyphenyl)propane,2,2′-bis(4-acryloxydiethoxyphenyl)propane,2,2′-bis[3(4-phenoxy)-2-dydroxypropane-1-methacrylate]propane.

The liquid component also contains an amine that is capable of forming asalt bridge between the calcium ions in the dentin and acrylic ormethacrylic esters. An example of a methacrylate ester isBis[2-(methacryloyloxy)ethyl]phosphate (BisMEP). The preferred aminesinclude but are not limited to aromatic amines such as4-(dimethylamino)benzoic acid (DMABA) and ethyl 4-dimethylaminobenzoate(EDMAB). The selection of the appropriate amine is critical. Unlikeother amines found in other dual-cure (chemical- and visible-lightphoto-curing functions together in one formulation) and photo-curedental and biomedical adhesive materials, the amine used in thepreferred embodiment (EDMAB) is stable in an acidic environment.

Furthermore, although some aromatic amines, such as DMABA and EDMAB,have been experimentally determined to be effective at permittingadherence of the polymerizable acrylate to dentin, others, such as2,2′-(p-tolylimino)diethanol (P-TID) is not effective.

In addition to the acrylates and amines, the liquid component of theinventive formulation contains one or more acrylic ester or methacrylicester. The esters function as an ester and as an acrylic or methacrylatecompound and form a cross-link between the polymerizable acrylic ormethacrylate compounds. In the preferred embodiment, dipentaerthritolpentaacrylate esters (SR 399 LV) are used as this cross-linker. SR 399LV is stable in an acid-polymerizable formula that contains an acid suchas Bis[2-(methacryloyloxy)ethyl]phosphate (BisMEP) and an amine basesuch as ethyl-4-dimethylaminobenzoate (EDMAB). SR 399 LV is easilyblended and co-polymerized with other methacrylates, such as2,2-Bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl]propane (BisGMA),hydroxyethylmethacrylate (HEMA) and triethyleneglycol dimethacrylate(TEGDMA), in the polymerizable formula. The incorporation ofdipentaerthritol pentaacrylate esters (SR 399 LV) would self-etch hardtissues (such as enamel, dentin, and bone) and crosslink the resinmatrix upon setting, which enhances the resin matrix upon polymerization(setting).

The powder component of the inventive composition contains many fillermaterials, which include glass powder of various particles sizes and oneor more fluoride releasing agents. The glass particles not only improvethe physical and mechanical properties of the composition but also serveas the base for the acid-base reaction. The powder component may alsocontain other filler materials such as Barium, Aerosil 200, Pigments,Silica, Alumina, Aluminum Fluoride, Calcium Fluoride, Sodium Fluoride,Aluminum Phosphate, Calcium, Strontium, Zinc, Sodium, Potassium,Lanthanum, Alumino-silicates, other metal oxides, metal fluorides andmetal phosphates

The adhesive composition also uses at least one initiator to permitphoto or chemical initiation of curing, which could be incorporated intoeither the liquid component or the powder component. The formulationmay, additionally, contain a co-initiator to accelerate the curingprocess. In the preferred embodiment, both a light-curing initiatorcamphorquinone (CQ) and a self-curing initiator (BPO) are used. A curinginhibitor, such as BHT, may also be included in the adhesive compositionin order to have a more controlled setting time.

Despite the chemicals identified in the preferred embodiments, theinventive formulation also contemplates that other chemicals, withsimilar characteristics, can be used. For example, in place of BisMEP, 4methacryloxyethyltrimellitic anhydride, biphenyldimethacrylate, ethyleneglycol methacrylate phosphate or other esters of methacrylate can beused. Similarly, other photo-initiators or chemical initiators, otherthan CQ can be used, such as diphenyl(2,4,6-trimethylbenzoyl)phosphineoxide. Also, in place of DMABA, other amines could be substituted, suchas ethyl 4-dimethylaminobezoate (EDMAB). Similarly,urethanedimethacrylate can be substituted for BisGMA. Otherdimethacrylate or multimethacrylate diluents can be used instead ofTEGDMA, such as trimethylpropane trimethacrylate.

For either dental or biomedical applications, each compound of thepreferred formulation will fall within the following ranges by weight.

Liquid Part

Chemical Formulation weight range (%) HEMA (20-50) TEGDMA (10-30) BisMEP (5-25) SR 399 LV  (5-25) BisGMA  (5-30) EDMAB (1-8) CQ (0.1-0.8)BHT(inhibitor) (0.01-0.06)

Powder Part:

Chemical Formulation weight range (%) GI SP2034 (70-95) BPO (1-5) BaGlass (1-5) Aerosil 200 (1-5) Pigment (0.001-0.01) 

Paste:

The powder and liquid were mixed in a powder: liquid ratio of 3:1 byweight to form a paste and chemically hardened (set) 4 to 4.5 minuteslater at 37° C. Although, the inventive adhesive composition may be usedfor many dental and medical applications, for illustrative purposes, thefollowing examples shows the inventive adhesive material being used as adental restoration materials and as luting cement. A preferredformulation of the invention composition for use as a dental restorativeand luting cement includes the following in the liquid and powdercomponents:

Liquid Component

Preferred Percentage Acronym Full Chemical Name Source by Weight HEMAHydroxyethylmethacrylate Aldrich ® 33.68% TEGDMA Triethyleneglycoldimethacrylate Aldrich ® 20.00% BisMEP Bis[2- Aldrich ® 20.00%(methacryloyloxy)ethyl]- phosphate SR 399 LV Dipentaerthritolpentaacrylate Sartomer ™ 10.00% esters BisGMA 2,2-Bis[4-(2-hydroxy-3-Aldrich ® 10.00% methacryloxypropoxy)phenyl- ]propane EDMABEthyl-4-Dimethylaminobenzoate Aldrich ®  6.00% BHT2,6-Di-tert-butyl-4-methylphenol Aldrich ®  0.02% CQ CamphorquinoneAldrich ®  0.30% Total = 100%

Powder Component

Preferred Percentage by Acronym Full Chemical Name Source Weight GISP2034 Glass powder TF grind Specialty 93.998%  Glass Products Inc.Pigment Phthalocyanine green 7 Ultradent 0.002%  Products Inc. BPODipentaerthritol Aldrich ® 2.00% pentaacrylate esters Ba Glass 7%silanated 0.7 μm Ba Esstech, Inc. 2.00% glass Aerosil 200 Aerosil A200Degussa 2.00% Total = 100%

It is relatively easy to prepare compounds from this formula. The powderand liquid were mixed in a powder:liquid ratio of 3:1 by weight. Mixingrequires thorough incorporation and blending of the separate powder andliquid components. After mixing, the paste sets (hardens) by way of anacid/base reaction and a free-radical polymerization reaction in 4 to4.5 minutes at 37° C.

When used as dental restorative, the liquid and powder components may bemixed and applied to the tooth structure immediately in one step andsimply wait for the restorative to set. Alternatively, the liquid andpowder components may be mixed and placed onto the tooth in anincremental fashion. For example, mixing a small amount of power andliquid components in the same 3:1 ratio by weight and apply the paste tothe tooth surface. Once the layer of paste hardens, a subsequent coat ofadhesive may be mixed and applied to the tooth. This incrementalbuild-up of adhesive materials allows the tooth to be restored itsphysiological shape.

Example 1 Properties of the Adhesive Composition as Dental RestorativeMaterials

The preferred inventive formulation is tested in the lab as a dentalrestorative material. Laboratory tests shows that the incorporation ofthe multi-functional acrylate cross-linking compound dramaticallyenhanced the physical and mechanical properties of the final set in theprototype dental material. When using this formula as a bonding agent,the clinical pre-treatment techniques of acid etching and priming thetooth structure are not necessary. The material was tested against otherclasses of dental materials commonly used as temporary fillings. Thosematerials were FUJI IX™ GP fast (GC America, IL), KETAC-MOLAR™ (3M™ESPE, MN), and IRM (Dentsply Caulk, DE). The tests used were hardness(Knoop), compressive strength, diametral tensile strength (DTS),flexural strength, and dentin shear bond strength. Table 1 belowprovides the results of those tests.

TABLE 1 Physical property tests of inventive formulation as applied to adental dressing. Shear Dentin Compressive Flexural Bond Dental HardnessStrength DTS Strength Strength Material (KHN) (MPa) (MPa) (MPa) (MPa)Inventive 36.6 (3.3) 162.9 (19.2) 27.67 (2.3)  82.1 12.2  formulation(5.3) (4.2) FUJI IX ™ 51.9 (2.3) 167.8 (29.4) 18.8 (3.8) 18.2 6.0 GP(3.2) (2.0) IRM ® 11.4 (1.6)  57.8 (10.9)  7.9 (0.9) 15.9 Not (1.7)tested KETAC- 45.1 (9.4) 149.1 (40.8) 24.8 (4.3) 17.3 3.9 MOLAR ™ (6.7)(1.2)

The inventive formulation proved to have properties that were comparableor better than those of the materials tested. Placement of the inventiveformulation on teeth requires minimal surface preparation and fewersteps for application, such as acid etching, priming, or use of bondingagents, resulting in less clinical time. In addition, the inventiveformulation releases fluoride. Table 2 presents the results offluoride-release tests.

TABLE 2 Cumulative fluoride release after 385 hours. Dental MaterialFluoride (ppm) Inventive Formulation 159.10 FUJI IX ™ GP 176.05Ketac-Bond 201.29 IRM ® 0

Method of Use as Luting Cement for Bonding Fixed Dental ProstheticDevices:

The inventive formulation may also be used as luting cement, for bondingfixed dental prosthetic devices, such as inlays, onlays, laminateveneers, bridges and crowns (including porcelain and porcelain fused tometal restorations), to dentin and enamel.

Example 2 Properties as Luting Cement for Bonding Ceramic DentalProsthetic Devices

The preferred formulation of the inventive composition previously statedwas also tested as luting cement for bonding fixed dental prostheticdevices.

Shear bond strengths (SBS) of DENTSTAT™ (the preferred inventiveformulation) and five commercially available luting cements to threetypes of ceramic substrates were determined (Table 3). Ten specimens ofeach material were tested.

TABLE 3 Luting cements and ceramic materials used in this study.Manufacturers Luting cements DENTSTAT ™ Ultradent Products, Inc, SouthJordan, UT MultiLink Automix Ivoclar/Vivadent, Schaan, LiechtensteinAegis C&B BOSWORTH ® Co., Skokie, IL PANAVIA 21 ® Kuraray America Inc,New York, NY Maxcem Kerr Co, Orange, CA NX3 Kerr Co, Orange, CA Ceramicmaterials IPS Empress CAD Ivoclar/Vivadent, Schaan, LiechtensteinVitablocs Mark III Vident, Brea, CA Paradigm C 3M ™/ESPE Corporation,St. Paul, MN

Ceramic blocks provided by the manufacturers were used withoutmechanical modification. All ceramic surfaces were treated usingporcelain etching gel (Pulpdent Co. Watertown, Mass.) and silanatedfollowing the manufacturers' instructions.

A #4 gelatin capsule (Torpac, Inc., Fairfield, N.J.) was half-filledwith a resin composite (P60, 3M™ ESPE, St. Paul, Minn.) and lightactivated for 40 seconds using a curing light (Spectrum 800,Dentsply/Caulk, Milford, Del.). The remainder of the capsule was filledwith the dental luting cement being tested, placed against the ceramictest surface, and stabilized with finger pressure. Excess material wasremoved from the base of the capsule, and the luting cement was allowedto set at room temperature (23±1° C.) for 10 minutes. The specimens werestored in 37±1° C. deionized water for 24 hours.

The specimens were tested to failure in shear with a testing machine(MTS, Alliance RT/5, MTS Corporation, Eden Prairie, Minn.) using acrosshead speed of 0.5 mm/min. Mean shear bond strengths (SBS) andstandard deviations were calculated, and means were analyzedstatistically using one-way ANOVA and Tukey's Test. The mode of failurewas determined for each specimen by visual examination.

The results are presented in the Table 4. Failures occurred all withinthe ceramic materials. The mean SBS for DENTSTAT™ was not significantlyhigher than the SBS for MultiLink Automix when bonding to IPS EmpressCAD and Paradigm C. However, the SBS of DENTSTAT™ was significantlyhigher than other luting cements when bonding to Vitablocs Mark III.Therefore, the SBS of DENTSTAT™ to all three ceramic substrates werecomparable to or greater than the other luting cements tested.

TABLE 4 Shear bond strength, means (st. dev.), MPa, n = 10. The SBS ofmaterials with the same letter within a column are not significantlydifferent (p > 0.05) IPS Vitablocs Empress CAD Mark III Paradigm CDENTSTAT ™ 25.3 (3.72) A 20.2 (4.59) A 22.2 (3.90) A MultiLink 21.5(4.98) A 11.8 (3.76) B 18.8 (4.34) A, B Automix Aegis C&B 12.8 (2.88) B,C 12.7 (2.35) B 14.2 (3.01) B, C PANAVIA 21 ® 12.3 (2.18) B, C 13.0(2.80) B 14.0 (4.12) B, C Maxcem 12.5 (4.21) B, C 11.6 (2.79) B 13.2(3.50) C NX3 12.0 (1.99) B, C 12.4 (4.28) B 12.1 (2.68) C

Example 3 Properties as Luting Cement for bonding Fixed Metal DentalProsthetic Devices

The shear bond strengths (SBS) of DENTSTAT™ and five commerciallyavailable luting cements to three metal substrates were determined(Table 5). Metal alloy specimens (approximately 8 mm long, 8 mm wide and4 mm thick) were fabricated per manufacturers' instructions using thelost wax technique. The metal specimens were mounted in autopolymerizingacrylic resin using cylindrical polytetrafluoroethylene molds with thetest surface of the specimens flush with the surface of the acrylic. Thetest surfaces were sandblasted.

TABLE 5 Luting cements and metal alloys used in this study.Manufacturers Luting cements DENTSTAT ™ Ultradent Products, Inc, SouthJordan, UT PANAVIA 21 ® Kuraray Medical Inc., New York, NY GC Fuji PlusGC America, Inc, Alsip, IL KETAC CEM ™ 3M/ESPE Corporation, St. Paul, MNACP C&B Harry J. Bosworth, Skokie, IL Durelon 3M/ESPE Corporation, St.Paul, MN Metal alloys FIRMILAY ® Jelenko, San Diego, CA REX4 ™ PentronAlloys, LLC, San Diego, CA OLYMPIA ® Jelenko, San Diego, CA

A #4 gelatin capsule (Torpac, Inc., Fairfield, N.J.) was half-filledwith a resin composite (P60, 3M™/ESPE Corporation, St. Paul, Minn.) andlight activated for 20 seconds using a curing light (Spectrum 800,Dentsply/Caulk, Milford, Del.). The remainder of the capsule was filledwith the dental luting cement being tested, placed against the metaltest surface, and stabilized with finger pressure. Excess material wasremoved from around the base of the capsule, and the luting cement wasallowed to set at room temperature (23±1° C.) for 10 minutes. Thespecimens were stored in 37±1° C. deionized water for 24 hours beforetesting.

The specimens were tested to failure in shear with a testing machine(MTS, Alliance RT/5, MTS Corporation, Eden Prairie, Minn.) using acrosshead speed of 0.5 mm/min. Mean shear bond strengths (SBS) andstandard deviations were calculated, and means were analyzedstatistically using one-way ANOVA and Tukey's Test. The results arepresented in the Table 6. The shear bond strengths of DENTSTAT™ to REX4™and OLYMPIA® were comparable to or greater than those of the otherproducts. Its bond strength to Firmilay was comparable to those of threeother cements.

TABLE 6 Shear bond strength means and standard deviations, (MPa), n =10. Firmilay ® Rex4 ™ Olympia ® DentStat ™ 4.0 (0.75) C, D 15.0 (3.65) A12.9 (1.33) A Panavia 21 ® 9.4 (2.70) A 13.2 (2.60) A 12.5 (1.63) A GCFuji Plus 6.7 (1.91) B 14.6 (2.17) A 13.3 (2.00) A Ketac Cem ™ 4.7(1.87) B, C  5.9 (2.13) B  5.6 (2.10) B ACP C&B 9.1 (0.94) A  7.3 (0.45)B  7.5 (0.40) B Durelon 5.5 (1.50) B, C  4.9 (1.13) B, C  5.7 (1.20) BZnPO₄ 2.1 (0.68) D  2.8 (0.51) C  2.6 (0.41) C The SBS of the materialswith the same letter within a column are not significantly different(p > 0.05)

Method of Use as Luting Cement for Bonding Orthodontic Brackets toEnamel:

The inventive formulation may also be used as a luting cement forbonding orthodontic brackets to enamel.

Example 8 Inventive Formulation Used as a Luting Cement for BondingOrthodontic Brackets to Enamel

The shear bond strengths (SBS) to tooth enamel of DENTSTAT™ and fivecommercially available orthodontic luting cements were determined. Eachbrand (Table 7) was designated as an experimental group with tenspecimens in each group.

TABLE 7 Orthodontic luting cements used in this study. Luting cementsManufacturers DENTSTAT ™ Ultradent Products, Inc, South Jordan, UTTransbond XT 3M/Unitek Monrovia, CA Heliosit Ivoclar/Vivadent, Schaan,Liechtenstein Aegis Ortho BOSWORTH ® Co., Skokie, IL GC Fuji LC GCAmerica Inc, Alsip, IL Ortho Choice Pulpdent Co. Watertown, MA

Sixty extracted, noncarious human molar teeth were used for the bondstrength test. Surface debris was manually removed from the teeth, andthe teeth were stored in a 0.5 percent aqueous solution of Chloramine-T(Sigma-Aldrich, St. Louis, Mo. 63178) prior to specimen preparation.During specimen fabrication, the enamel surfaces of the teeth weretreated following manufacturers' instructions for luting orthodonticbrackets. An orthodontic bracket (SYNERGY®, RMO® Roth straight wire,Rocky Mountain Orthodontics, Denver, Colo.) was positioned on theprepared enamel surface with one of the luting cements and photo-curedfor 40 seconds (ten seconds on each side of the bracket) using a dentalcuring light (Spectrum 800, Dentsply/Caulk). The specimens were storedin 37±1° C. deionized water for 24 hours before testing.

The specimens were tested to failure in shear with a testing machine(MTS, Alliance RT/5) using a crosshead speed of 0.5 mm/min. Followingshear bond strength testing, all specimens were examined at 8×magnification using a stereomicroscope to determine the mode of failurebetween the luting cement and enamel. Mean SBS and standard deviationswere calculated, and means were analyzed statistically using one-wayANOVA and Tukey's Test.

The results are presented in the Table 8. The shear bond strength ofDENTSTAT™ to enamel was significantly higher than those of the otherluting cements. All failures were at the cement/enamel interface.

TABLE 8 Shear bond strength to enamel, means (st dev), n = 10. SBS (MPa)DentStat ™ 12.7 (2.13) A Transbond XT 11.8 (2.25) B Heliosit 10.7 (2.88)B Aegis Ortho 10.6 (1.72) B GC Fugi LC 9.59 (1.21) B Ortho Choice 9.39(1.29) B Materials with the same letter are not significantly different(p > 0.05).

Because its superior mechanical properties, the inventive compositionmay be used in many other dental or biomedical applications, such asstint for stabilizing avulsed, inverted, or luxated teeth, or as bonecement, for bonding implant prostheses and skull implants to bone, orliner and base under amalgam dental restorations.

Obviously, many modifications and variations of the present inventionare possible in light of the above teaching. It is therefore to beunderstood that, within the scope of the appended claims, the inventionmay be practiced otherwise than as specifically described. Theprinciples described above can be readily modified or adapted forvarious applications without departing from the generic concept, andtherefore such adaptations and modifications are intended to becomprehended within the meaning and range of equivalents of the enclosedembodiments. It is to be understood that the terminology and phraseologyherein is for the purpose of description and not of limitation.

1. An adhesive composition comprising a mixture of: a. one or morepolymerizable acrylic or methacrylate compounds; b. one or morehydrophilic acrylate or methacrylate compounds; c. one or more calciumreactive amines; d. one or more acrylic or methacrylic esters, whereinsaid esters form a multifunctional acrylic cross-link between saidpolymerizable acrylic or methacrylic compounds; e. one or morepolymerization initiators; and f. filler materials, wherein said fillermaterials contain glass powder and fluoride-containing compounds.
 2. Theadhesive composition of claim 1, wherein said polymerizable acryliccompounds are: ethyl acrylate, propyl acrylate, isopropyl acrylate,2-hydroxyethyl acrylate, hydroxypropyl acrylate, tetrahydrofurfurylacrylate, glycidyl acrylate, glycerol mono- and di-acrylate,ethyleneglycol diacrylate, polyethyleneglycol diacrylate, neopentylglycol diacrylate, trimethylolpropane triacrylate, mono-, di-,tri-acrylate, mono-, di-, tri-, and tetra-acrylates of pentacrythritoland dipentaerythritol, 1,3-butanediol diacrylate,1,4-butanedioldiacrylate, 1,6-hexane diol diacrylate,2,2′-bis[3(4-phenoxy)-2-hydroxypropane-1-acrylate]propane, 2,2′bis(4-acryloxyphenyl)propane,2,2′-bis[3(4-phenoxy)-2-hydroxypropane-1-acrylate]propane,dipentaerthritol pentaacrylate esters (SR 399) and dipentaerthritolpentaacrylate esters (SR 399 LV).
 3. The adhesive composition of claim1, wherein said polymerizable methacrylate compounds include:methacrylates, ethyl methacrylate, propyl methacrylate, isopropylmethacrylate, tetrahydrofurfuryl methacrylate, glycidyl methacrylate,the diglycidyl methacrylate of bis-phenol A(2,2-Bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl]propane) (BisGMA),glycerol mono- and di-methacrylate, ethyleneglycol dimethacrylate,polyethyleneglycol dimethacrylate, triethylene glycol dimethacrylate(TEGDMA), neopentylglycol dimethacrylate, trimethylol propanetrimethacrylate, mono-, di-, tri-, and tetra-methacrylates ofpentacrythritol and dipentaerythritol, 1,3-butanediol dimethacrylate,1,4-butanediol dimethacrylate, Bis[2-(methacryloyloxy)ethyl]phosphate(BisMEP),1,6-hexanediol dimethacrylate,2-2′-bis(4-methacryloxyphenyl)propane,2,2′-bis[4(2-hydroxy-3-methacryloxy-phenyl)]propane, 2,2′bis[4(2-hydroxy-3acryloxyphyenyl)propane,2,2′-bis(4-methacryloxyethoxyphenyl)propane,2,2′-bis(4-acryloxyethoxyphenyl)propane,2,2′-bis(4-methacryloxypropoxyphenyl)propane,2,2′-bis(4-acryloxypropoxyphenyl)propane,2,2′-bis(4-methacryloxydiethoxyphenyl)propane,2,2′-bis(4-acryloxydiethoxyphenyl)propane,2,2′-bis[3(4-phenoxy)-2-dydroxypropane-1-methacrylate]propane.
 4. Theadhesive composition of claim 1, wherein said hydrophilic acrylatecompounds are 2-hydroxyethyl acrylate, and hydroxypropyl acrylate. 5.The adhesive composition of claim 1, wherein said methacrylate compoundis hydroxyethylmethacrylate (HEMA).
 6. The adhesive composition of claim1, wherein said calcium reactive amines areethyl-4-Dimethylaminobenzoate (EDMAB) and 4-(dimethylamino) benzoic acid(DMABA).
 7. The adhesive composition of claim 1, wherein said acrylicester is SR 399 LV.
 8. The adhesive composition of claim 1, wherein saidmethacrylic ester is bis[2-(methacryloyloxy)ethyl]phosphate (BisMEP). 9.The adhesive composition of claim 1, wherein said polymerizationinitiator is chemical initiator, photo-initiator, or combinationthereof.
 10. The adhesive composition of claim 9, wherein said chemicalinitiator is BPO.
 11. The adhesive composition of claim 9, wherein saidphoto-initiator are selected from the group consisting of diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide and camphorquinone (CQ).
 12. Theadhesive composition of claim 1, wherein said glass powder is a mixtureof glass particles 0.02 to 40 microns in size.
 13. The adhesivecomposition of claim 1, wherein said adhesive is a bonding agent betweena substrate and a hard tissue.
 14. The composition of claim 13, whereinsaid hard tissue is selected from the group consisting of enamel, bone,and dentin.
 15. The adhesive composition of claim 13, wherein saidsubstrate is selected from the group consisting of acrylates, compositeresins, ceramics, and metals.
 16. The adhesive composition of claim 1,wherein said adhesive is a bonding agent that can be used for thestabilization of avulsed, inverted, or luxated teeth to adjacentunaffected teeth.
 17. The adhesive composition of claim 1, wherein a.said polymerizable methacrylate compound is TEGDMA; b. said hydrophilicmethacrylate compound is HEMA; c. said calcium reactive amine is EDMAB;d. said acrylic or methacrylic ester are BisMEP and SR399LV; e. saidpolymerization initiator are CQ and BPO; f. said glass powder is BaGlass. g. said filler materials are GI SP2034, Ba Glass, Aerosil 200;and h. and fluoride-containing compound is GI SP
 2034. 18. A method ofdental restoration using the adhesive composition of claim 1, comprisinga. blending said mixture thoroughly at a powder to liquid ratio of 3:1by weight; b. applying said mixture to a dental substrate; c. allowingsaid mixture to harden; d. repeating steps a-c until said mixturesresembles the physiological shape of the missing teeth.
 19. The adhesivecomposition of claim 1, wherein said filler materials comprise Barium,Aerosil 200, Pigments, Calcium Fluoroaluminosilicate glass, Silica,Alumina, Aluminum Fluoride, Calcium Fluoride, Sodium Fluoride, AluminumPhosphate, Calcium, Strontium, Zinc, Sodium, Potassium, Lanthanum, andAlumino-silicates or any combination thereof.